The purpose of this project is to identify the determinants of non- insulin-dependent diabetes (NIDDM), various types of arthritis, and gallbladder disease, and elucidate the natural history of the diseases. Genetic and environmental risk factors for NIDDM have been studied in the Pima Indians. The residents of the study area, approximately 5000 people, have participated in a longitudinal population study since 1965, allowing observations of the natural history of diabetes mellitus. Risk factors for obesity, hypertension, and cholelithiasis are also studied, along with the relationships of these diseases to diabetes and their effects on mortality rates. The genetics of diabetes is studied by means of family studies and relationships of genetic markers to disease. The roles of obesity, serum insulin concentrations, impaired glucose tolerance, occupational and leisure-time physical activity and diabetes in relatives are assessed. The age-specific incidence rates of NIDDM have been increasing among the Pima Indians. Analyzed by birth cohort, age-sex-adjusted incidence rates have increased by an average of 13% in each successive decade of birth year, suggesting that exposure to diabetogenic lifestyle factors may have increased progressively over the 80-year span of birth cohorts examined. Follow-up for development of diabetes after measurement of body size by a variety of methods indicated that several methods were equivalent as predictors. Thus simple measures such as waist circumference, weight, and body mass index may be just as useful as more complicated measures such as estimated percent body fat by bioelectrical impedance. The association of diabetic nephropathy and diabetes was studied in Pima Indian pedigrees. The presence of nephropathy in a parent with diabetes relative to diabetes alone was associated with 2.5 times the odds of diabetes in the offspring. These results are compatible with the hypothesis that the susceptibility to renal disease in the parents and to diabetes in the offspring are due to shared familial environmental factors or the same gene or set of genes.